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During the Mexican era, a trail or road ran between the homes of the Peralta brothers, Domingo and Vicente. Domingo made his home along Codornices Creek near what is today the intersection of Sacramento and Hopkins Streets in Berkeley. Vicente's home was situated along Temescal Creek near what is today the intersection of 55th Street and Telegraph Avenue in North Oakland. The route of this early predecessor road, which came to be called the "Temescal Road",[3] is depicted on the first official plat map of the area, Kellersberger's Map. A trace of it survives today as Racine Avenue in North Oakland.

During the 1850s, Francis Shattuck and three others laid claim to four adjoining strips of land in what is now downtown Berkeley. The dividing line between the parcels claimed by Shattuck and his brother-in-law George Blake became the alignment of a new county road whose construction the Board of Supervisors assigned to Francis Shattuck, a member of the board. The new road was laid out from where Strawberry Creek intersected the old Temescal Road, thence along the new alignment, extending southward to a gore point intersection with the Telegraph Road (today's Telegraph Avenue). The road became known as "Shattuck's Road". Francis Shattuck built his new home above the north bank of Strawberry Creek at the northern terminus of the county road, which was also the northern bound of Shattuck's claim, along the alignment of what is now Addison Street. The creek and Shattuck's home were situated along what is now Allston Way.

In 1866, the College Homestead Association, an organization established to raise funds for the new site of the College of California, filed a plat map with the object of selling parcels of land near the site of the present University of California. This map proposed names for several streets in a grid pattern, incorporating the alignment of Shattuck's Road, but designating it "Guyot Street". The name never stuck. By the time of the incorporation of the Town of Berkeley in 1878, Shattuck's Road had become Shattuck Avenue. By that time also, it had been extended northward to Rose Street. Additionally, the Central Pacific, at Shattuck's urging, had constructed its Berkeley Branch Railroad which merged into Shattuck at Adeline Avenue. In later years, this line was assigned to the Southern Pacific and eventually electrified and extended. Streetcars and transbay trains of the competing Key System also ran on Shattuck in Berkeley.

Shattuck is an important north-south arterial roadway for northern Alameda County connecting the downtowns of Berkeley and Oakland. In the early 20th Century the road included commuter train and streetcar tracks.[4] Today BART carries commuters on the system's second most popular line underneath the pavement. This includes the Ashby and Downtown Berkeley stations. The Downtown Berkeley is one of BART's most frequented stations and a transit hub for AC Transit and Bear Transit buses. Furthermore AC's 1R BRT line terminates at this location.